Determination of Diffusion Constants for Metabolites in Multicell Tumor Spheroids

Abstract

Multicell tumor spheroids (MTS) exhibit many of the characteristics of tumors, including central necrosis, heterogeneities in proliferative status and clonogenic capacity, and subpopulations of radiation and chemotherapeutic resistant cells (Freyer and Sutherland, 1980; Sutherland and Durand, 1976). In tumors, control of most of these parameters appears to be due to low molecular eight nutrients such as oxygen and glucose. Tannock (1976) suggested that loss of proliferative activity was correlated with the oxygen diffusion distance. Low values of oxygen partial pressure in tumors are common (Thews and Vaupel, 1974), as are low pH values (Vaupel et al., 1981). Tumor extracellular fluid has been shown to contain low levels of glucose (Guillino, 1975). Most tumors are very heterogeneous with respect to the local microenvironment (Mueller-Klieser et al., 1980) due to the random structure and chaotic functioning of the vascular system. Thus, it has been proven difficult to establish precisely which nutrient(s) are critical for cellular proliferation and viability in vivo.